X-132890476-C-T

Variant names:

• chrX-132890476-C-T
• rs7892161
• NM_001394073.1:c.947+66332G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001394073.1(HS6ST2):​c.947+66332G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.57 (13694 hom., 14838 hem., cov: 18)
  • Failed GnomAD Quality Control
• Consequence: HS6ST2 NM_001394073.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359
• Publications: 2 publications found

Genes affected

HS6ST2 (HGNC:19133): (heparan sulfate 6-O-sulfotransferase 2) Heparan sulfate proteoglycans are ubiquitous components of the cell surface, extracellular matrix, and basement membranes, and interact with various ligands to influence cell growth, differentiation, adhesion, and migration. This gene encodes a member of the heparan sulfate (HS) sulfotransferase gene family, which catalyze the transfer of sulfate to HS. Different family members and isoforms are thought to synthesize heparan sulfates with tissue-specific structures and functions. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HS6ST2 Gene-Disease associations (from GenCC):

• Paganini-Miozzo syndrome

  Inheritance: Unknown, XL Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394073.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS6ST2	NM_001394073.1	MANE Select	c.947+66332G>A		intron	N/A	NP_001381002.1	Q96MM7-4
	HS6ST2	NM_001077188.2		c.947+66332G>A		intron	N/A	NP_001070656.1	Q96MM7-4
	HS6ST2	NM_001394074.1		c.947+66332G>A		intron	N/A	NP_001381003.1	Q96MM7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS6ST2	ENST00000370833.7	TSL:5 MANE Select	c.947+66332G>A		intron	N/A	ENSP00000359870.3	Q96MM7-4
	HS6ST2	ENST00000406696.5	TSL:1	c.509+66332G>A		intron	N/A	ENSP00000384013.5	Q96MM7-3
	HS6ST2	ENST00000521489.5	TSL:5	c.947+66332G>A		intron	N/A	ENSP00000429473.1	Q96MM7-4

Frequencies

GnomAD3 genomes AF: 0.567 AC: 59233 AN: 104427 Hom.: 13690 Cov.: 18

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.540

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.567 AC: 59284 AN: 104480 Hom.: 13694 Cov.: 18 AF XY: 0.540 AC XY: 14838 AN XY: 27460

African (AFR) AF: 0.786 AC: 22500 AN: 28608

American (AMR) AF: 0.365 AC: 3595 AN: 9850

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1183 AN: 2548

East Asian (EAS) AF: 0.466 AC: 1485 AN: 3190

South Asian (SAS) AF: 0.489 AC: 1047 AN: 2143

European-Finnish (FIN) AF: 0.513 AC: 2631 AN: 5128

Middle Eastern (MID) AF: 0.587 AC: 111 AN: 189

European-Non Finnish (NFE) AF: 0.506 AC: 25669 AN: 50761

Other (OTH) AF: 0.540 AC: 775 AN: 1436

Alfa AF: 0.543 Hom.: 3907

Bravo AF: 0.568

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.43
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7892161; hg19: chrX-132024504;